Angular multiplexed optical coherence tomography systems and methods

ABSTRACT

Angle multiplexed optical coherence tomography systems and methods can be used to evaluate ocular tissue and other anatomical structures or features of a patient. The angle multiplexed optical coherence tomography system includes a light source, an optical assembly for obtaining a plurality of sample beams corresponding to respective anatomical locations of the eye of the patient, where individual sample beams are associated with a respective non-zero angle relative to a reference beam, and a detection mechanism that detects individual unique interference patterns respectively provided by the plurality of sample beams, for simultaneous evaluation of the anatomical locations.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation application under 35 USC § 120 ofU.S. patent application Ser. No. 15/343,750, filed Nov. 4, 2016, nowpending, which is a continuation application under 35 USC § 120 of U.S.patent application Ser. No. 14/864,730, filed Sep. 24, 2015 and issuedon Nov. 8, 2016 as U.S. Pat. No. 9,486,137, which is a continuationapplication under 35 USC § 120 of U.S. patent application Ser. No.14/199,161, filed Mar. 6, 2014 and issued on Dec. 1, 2015 as U.S. Pat.No. 9,198,573, which claims priority to U.S. Provisional application No.61/794,276, filed on Mar. 15, 2013. The entire contents of the aboveapplications are all incorporated herein by reference.

BACKGROUND OF THE INVENTION

Optical Coherence Tomography (OCT) is used in the ophthalmic industry inpachymetry, anterior chamber depth, axial length, and retinal imagingapplications. Known OCT systems typically use either a time domain or aspectral domain technology to provide line of sight length opticalanalogs of the echoes in ultrasonic imaging via homodyne detection. Withthe use of broadband sources, there is homodyne signal amplitude whenthe reference and signal beams are sufficiently close in optical delay.Time domain and spectral domain OCT use collinear reference and signalbeams to achieve a detectable interference that includes the depthinformation.

Currently known OCT systems involving axial measurements may benegatively impacted by axial or transverse eye movement during themeasurement. For example, existing time domain measurements techniquesused to measure axial length may be prone to such errors where a mirrormust be physically scanned to scan the depth range. Relatedly, manycurrently known spectral domain methods typically do not afford thedepth of range desirable for axial length measurements because the depthrange is determined by the spectral resolution of thespectrometer/detector combination. In many instances, the range whichmay be obtained from such instruments is effectively limited to amaximum of about 5 mm. In addition, existing spectral domain OCTtechniques may be prone to ghost images.

Some have proposed multiple spectral domain OCT systems with offsetaxial depth locations, single or multiple SLD sources for use withseparate spectrometers for each depth, and the implementation ofswitchable time delay references (e.g., using fiber switches withdifferent length fibers) for spectral domain OCT to address theselimitations. However, many time such proposals suffer from high costs.

Hence, although current techniques may provide real benefits to those inneed, still further improvements may be desirable. Embodiments of thepresent invention provide solutions to at least some of theseoutstanding needs.

BRIEF SUMMARY OF THE INVENTION

Embodiments of the present invention encompass the use of highly preciseOCT techniques, which are particularly useful for noninvasive evaluationof the optical characteristics of the human eye or other tissues, andcan be used to enhance or supplement other optical evaluation modalitiessuch as topography and/or wavefront sensing. For example certain OCTapproaches can be used to ascertain a range distance for use withtopography procedures, and/or to measure internal distance featurespresent within the eye. In some cases, OCT techniques as discussedherein can be used to precisely evaluate the distance between an opticalelement (e.g. final lens) of a optical system device and an opticalfeature (e.g. corneal apex) of the eye. Accordingly, embodiments of thepresent invention encompass systems and methods for obtaining extremelylow surface uncertainties, for example on the order of a fraction of amicron. Topography measurements obtained in conjunction with suchtechniques can provide a highly accurate diagnostic evaluation for apatient eye, and such approaches are well suited for use in evaluatingcorneal morphology and/or pathology, at times before, during, or aftersurgery.

Embodiments of the present invention encompass systems and methods forevaluating optical tissue in an eye of a patient and for other medicalimaging purposes. Exemplary techniques involve simultaneously monitoringa wide depth of range across patient tissue structure. In some cases,opthalmological evaluation techniques as discussed herein can be used toobtain volumetric three dimensional images of the human eye. Exemplarytechniques involve simultaneously monitoring multiple depth ranges withoffsets, optionally with a single detector. Such approaches can ensuretime coincidence and also lower hardware costs. In some cases, exemplarytechniques do not involve the use of complicated IR detectors or sweptlight sources. In some cases, exemplary techniques do not involve theuse of devices requiring a complex assembly of moving parts orcomplicated data acquisition and processing routines. According to someembodiments, angularly multiplexed signals from different depths orspatial locations can be combined on a single detector to providesimultaneous homodyne detection. According to some embodiments, suchcombination methods can provide a depth span for each angularly encodedsignal, making it possible to simultaneously measure over a largeeffective depth of range or to simultaneously measure at differentspatial locations.

In one aspect, embodiments of the present invention encompass anglemultiplexed optical coherence tomography systems and methods forevaluating an eye of a patient. Exemplary systems include a lightsource, and an optical assembly for obtaining a plurality of samplebeams corresponding to respective anatomical locations of the eye of thepatient. Individual sample beams are associated with a respective anglerelative to a reference beam. Systems can also include a detectionmechanism that detects individual unique interference patternsrespectively provided by the plurality of sample beams, for simultaneousevaluation of the anatomical locations. According to some embodiments,individual sample beams provide respective unique interference spatialperiods at the detection mechanism. According to some embodiments,unique interference spatial periods are adjustable in response tochanges in respective sample beam angles relative to the reference beam.In some cases, systems include one or more collimation lenses thatdirect combined sample-reference beam pairs toward the detectionmechanism. In some cases, systems and methods provide an accuracy forrange finding on the order of 10 microns. In some cases, systems includea filter assembly that transmits transmits interference signals atspatial frequencies about a first sample-reference beam pair andsuppresses interference signals at spatial frequencies about a secondsample-reference beam pair.

In another aspect, embodiments of the present invention encompassoptical coherence tomography for evaluating an eye of a patient, whichinvolve a light source, and an optical assembly for obtaining a samplebeams corresponding to an anatomical location of the eye of the patient.The sample beam can be associated with an angle relative to a referencebeam. Systems and methods can also involve a lens that receives thesample beam and reference beam as a pair of beams combined at the angle,and directs the combined sample-reference beam pair toward a detectionmechanism that detects an interference pattern provided by the beam pairfor evaluation of the anatomical location.

In another aspect, embodiments of the present invention encompass anglemultiplexed optical coherence tomography systems and methods forevaluating an eye of a patient. Exemplary methods include obtaining aplurality of sample beams corresponding to respective anatomicallocations of the eye of the patient. Individual sample beams can beassociated with a respective angle relative to a reference beam. Methodsmay also include detecting individual unique interference patternsrespectively provided by the plurality of sample beams, and evaluatingthe eye of the patient based on the detected interference patterns. Insome cases, methods include positioning a corneal topography systemrelative to the eye based on the evaluation, and obtaining a cornealtopography measurement of the eye. In some cases, topographymeasurements can be performed without aligning the corneal topographysystem using corneal topography fiducials.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 to 15 depict aspects of angular optical coherence tomographysystems and methods according to embodiments of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention encompass systems and methods forthe topographical monitoring of optical or other patient tissue across awide depth of range in a simultaneous fashion. According to someembodiments, angular multiplexed optical coherence tomography (AMOCT)techniques can use non-collinear beams to produce a spatial interferencepattern with a unique carrier frequency. Such a frequency can bedetermined by the angle between the signal and reference beams. Multiplecarrier frequencies can be supported simultaneously on a single lineararray detector by assigning a unique angle to each unique signal beamand combining them with a single, common reference beam.

According to some embodiments, a detector can receive multiple signalfrequencies simultaneously, and the readout of a signal assigned to aspecific carrier frequency can be achieved by frequency filtering thecomposite signal. Having resolved the specific signals, the compositeecho signal can be constructed using prior knowledge about theirrespective time delays or spatial locations. The delays in the varioussignals may be distributed to provide a large effective depth rangeuseful in simultaneous anterior chamber depth (ACD), lens thickness,axial length, or other optical feature measurements. According to someembodiments, the signals may have similar delays but could samplevarious transverse locations simultaneously to provide multi-pointmeasurements such as multipoint pachymetry without the need for movingparts.

Embodiments of the present invention can be readily adapted for use withexisting laser systems and other optical diagnostic and treatmentdevices. Although system, software, and method embodiments of thepresent invention are described primarily in the context of a laser eyesurgery system, it should be understood that embodiments of the presentinvention may be adapted for use in alternative eye diagnostic andtreatment procedures, systems, or modalities, such as spectacle lenses,intraocular lenses, accommodating IOLs, contact lenses, corneal ringimplants, collagenous corneal tissue thermal remodeling, corneal inlays,corneal onlays, other corneal implants or grafts, and the like.Relatedly, systems, software, and methods according to embodiments ofthe present invention are well suited for customizing any of thesetreatment modalities to a specific patient. Thus, for example,embodiments encompass custom intraocular lenses, custom contact lenses,custom corneal implants, and the like, which can be configured to treator ameliorate any of a variety of vision conditions in a particularpatient based on their unique ocular characteristics or anatomy.Additionally, the ablation target or target shape may be implemented viaother non-ablative laser therapies, such as laser-incised customlenticule shapes and subsequent extraction and laser-based cornealincision patterns. Embodiments of the present invention are not limitedto ophthalmic uses and can include analysis of translucent biologicaltissues and inorganic materials.

Turning now to the drawings, FIG. 1 illustrates a laser eye surgerysystem 10 of the present invention, including a laser 12 that produces alaser beam 14. Laser 12 is optically coupled to laser delivery optics16, which directs laser beam 14 to an eye E of patient P. A deliveryoptics support structure (not shown here for clarity) extends from aframe 18 supporting laser 12. A microscope 20 is mounted on the deliveryoptics support structure, the microscope often being used to image acornea of eye E.

Laser 12 generally comprises an excimer laser, ideally comprising anargon-fluorine laser producing pulses of laser light having a wavelengthof approximately 193 nm. Laser 12 will preferably be designed to providea feedback stabilized fluence at the patient's eye, delivered viadelivery optics 16. The present invention may also be useful withalternative sources of ultraviolet or infrared radiation, particularlythose adapted to controllably ablate the corneal tissue without causingsignificant damage to adjacent and/or underlying tissues of the eye.Such sources include, but are not limited to, solid state lasers andother devices which can generate energy in the ultraviolet wavelengthbetween about 185 and 205 nm and/or those which utilizefrequency-multiplying techniques. Hence, although an excimer laser isthe illustrative source of an ablating beam, other lasers may be used inthe present invention.

Laser system 10 will generally include a computer or programmableprocessor 22. Processor 22 may comprise (or interface with) aconventional PC system including the standard user interface devicessuch as a keyboard, a display monitor, and the like. Processor 22 willtypically include an input device such as a magnetic or optical diskdrive, an internet connection, or the like. Such input devices willoften be used to download a computer executable code from a tangiblestorage media 29 embodying any of the methods of the present invention.Tangible storage media 29 may take the form of a floppy disk, an opticaldisk, a data tape, a volatile or non-volatile memory, RAM, or the like,and the processor 22 will include the memory boards and other standardcomponents of modern computer systems for storing and executing thiscode. Tangible storage media 29 may optionally embody wavefront sensordata, wavefront gradients, a wavefront elevation map, a treatment map, acorneal elevation map, and/or an ablation table. While tangible storagemedia 29 will often be used directly in cooperation with a input deviceof processor 22, the storage media may also be remotely operativelycoupled with processor by means of network connections such as theinternet, and by wireless methods such as infrared, Bluetooth, or thelike.

Laser 12 and delivery optics 16 will generally direct laser beam 14 tothe eye of patient P under the direction of a computer 22. Computer 22will often selectively adjust laser beam 14 to expose portions of thecornea to the pulses of laser energy so as to effect a predeterminedsculpting of the cornea and alter the refractive characteristics of theeye. In many embodiments, both laser beam 14 and the laser deliveryoptical system 16 will be under computer control of processor 22 toeffect the desired laser sculpting process, with the processor effecting(and optionally modifying) the pattern of laser pulses. The pattern ofpulses may by summarized in machine readable data of tangible storagemedia 29 in the form of a treatment table, and the treatment table maybe adjusted according to feedback input into processor 22 from anautomated image analysis system in response to feedback data providedfrom an ablation monitoring system feedback system. Optionally, thefeedback may be manually entered into the processor by a systemoperator. Such feedback might be provided by integrating the wavefrontmeasurement system described below with the laser treatment system 10,and processor 22 may continue and/or terminate a sculpting treatment inresponse to the feedback, and may optionally also modify the plannedsculpting based at least in part on the feedback. Measurement systemsare further described in U.S. Pat. No. 6,315,413, the full disclosure ofwhich is incorporated herein by reference.

Laser beam 14 may be adjusted to produce the desired sculpting using avariety of alternative mechanisms. The laser beam 14 may be selectivelylimited using one or more variable apertures. An exemplary variableaperture system having a variable iris and a variable width slit isdescribed in U.S. Pat. No. 5,713,892, the full disclosure of which isincorporated herein by reference. The laser beam may also be tailored byvarying the size and offset of the laser spot from an axis of the eye,as described in U.S. Pat. Nos. 5,683,379, 6,203,539, and 6,331,177, thefull disclosures of which are incorporated herein by reference.

Still further alternatives are possible, including scanning of the laserbeam over the surface of the eye and controlling the number of pulsesand/or dwell time at each location, as described, for example, by U.S.Pat. No. 4,665,913, the full disclosure of which is incorporated hereinby reference; using masks in the optical path of laser beam 14 whichablate to vary the profile of the beam incident on the cornea, asdescribed in U.S. Pat. No. 5,807,379, the full disclosure of which isincorporated herein by reference; hybrid profile-scanning systems inwhich a variable size beam (typically controlled by a variable widthslit and/or variable diameter iris diaphragm) is scanned across thecornea; or the like. The computer programs and control methodology forthese laser pattern tailoring techniques are well described in thepatent literature.

Additional components and subsystems may be included with laser system10, as should be understood by those of skill in the art. For example,spatial and/or temporal integrators may be included to control thedistribution of energy within the laser beam, as described in U.S. Pat.No. 5,646,791, the full disclosure of which is incorporated herein byreference. Ablation effluent evacuators/filters, aspirators, and otherancillary components of the laser surgery system are known in the art.Further details of suitable systems for performing a laser ablationprocedure can be found in commonly assigned U.S. Pat. Nos. 4,665,913,4,669,466, 4,732,148, 4,770,172, 4,773,414, 5,207,668, 5,108,388,5,219,343, 5,646,791 and 5,163,934, the complete disclosures of whichare incorporated herein by reference. Suitable systems also includecommercially available refractive laser systems such as thosemanufactured and/or sold by Alcon, Bausch & Lomb, Nidek, WaveLight,LaserSight, Schwind, Zeiss-Meditec, and the like. Basis data can befurther characterized for particular lasers or operating conditions, bytaking into account localized environmental variables such astemperature, humidity, airflow, and aspiration.

FIG. 2 is a simplified block diagram of an exemplary computer system 22that may be used by the laser surgical system 10 of the presentinvention. Computer system 22 typically includes at least one processor52 which may communicate with a number of peripheral devices via a bussubsystem 54. These peripheral devices may include a storage subsystem56, comprising a memory subsystem 58 and a file storage subsystem 60,user interface input devices 62, user interface output devices 64, and anetwork interface subsystem 66. Network interface subsystem 66 providesan interface to outside networks 68 and/or other devices, such as thewavefront measurement system 30.

User interface input devices 62 may include a keyboard, pointing devicessuch as a mouse, trackball, touch pad, or graphics tablet, a scanner,foot pedals, a joystick, a touchscreen incorporated into the display,audio input devices such as voice recognition systems, microphones, andother types of input devices. User input devices 62 will often be usedto download a computer executable code from a tangible storage media 29embodying any of the methods of the present invention. In general, useof the term “input device” is intended to include a variety ofconventional and proprietary devices and ways to input information intocomputer system 22.

User interface output devices 64 may include a display subsystem, aprinter, a fax machine, or non-visual displays such as audio outputdevices. The display subsystem may be a cathode ray tube (CRT), aflat-panel device such as a liquid crystal display (LCD), a projectiondevice, or the like. The display subsystem may also provide a non-visualdisplay such as via audio output devices. In general, use of the term“output device” is intended to include a variety of conventional andproprietary devices and ways to output information from computer system22 to a user.

Storage subsystem 56 can store the basic programming and data constructsthat provide the functionality of the various embodiments of the presentinvention. For example, a database and modules implementing thefunctionality of the methods of the present invention, as describedherein, may be stored in storage subsystem 56. These software modulesare generally executed by processor 52. In a distributed environment,the software modules may be stored on a plurality of computer systemsand executed by processors of the plurality of computer systems. Storagesubsystem 56 typically comprises memory subsystem 58 and file storagesubsystem 60.

Memory subsystem 58 typically includes a number of memories including amain random access memory (RAM) 70 for storage of instructions and dataduring program execution and a read only memory (ROM) 72 in which fixedinstructions are stored. File storage subsystem 60 provides persistent(non-volatile) storage for program and data files, and may includetangible storage media 29 (FIG. 1) which may optionally embody wavefrontsensor data, wavefront gradients, a wavefront elevation map, a treatmentmap, and/or an ablation table. File storage subsystem 60 may include ahard disk drive, a floppy disk drive along with associated removablemedia, a Compact Digital Read Only Memory (CD-ROM) drive, an opticaldrive, DVD, CD-R, CD-RW, solid-state removable memory, and/or otherremovable media cartridges or disks. One or more of the drives may belocated at remote locations on other connected computers at other sitescoupled to computer system 22. The modules implementing thefunctionality of the present invention may be stored by file storagesubsystem 60.

Bus subsystem 54 provides a mechanism for letting the various componentsand subsystems of computer system 22 communicate with each other asintended. The various subsystems and components of computer system 22need not be at the same physical location but may be distributed atvarious locations within a distributed network. Although bus subsystem54 is shown schematically as a single bus, alternate embodiments of thebus subsystem may utilize multiple busses.

Computer system 22 itself can be of varying types including a personalcomputer, a portable computer, a workstation, a computer terminal, anetwork computer, a control system in a wavefront measurement system orlaser surgical system, a mainframe, or any other data processing system.Due to the ever-changing nature of computers and networks, thedescription of computer system 22 depicted in FIG. 2 is intended only asa specific example for purposes of illustrating one embodiment of thepresent invention. Many other configurations of computer system 22 arepossible having more or less components than the computer systemdepicted in FIG. 2.

Referring now to FIG. 3, one embodiment of a wavefront measurementsystem 30 is schematically illustrated in simplified form. In verygeneral terms, wavefront measurement system 30 is configured to senselocal slopes of a gradient map exiting the patient's eye. Devices basedon the Hartmann-Shack principle generally include a lenslet array tosample the gradient map uniformly over an aperture, which is typicallythe exit pupil of the eye. Thereafter, the local slopes of the gradientmap are analyzed so as to reconstruct the wavefront surface or map.

More specifically, one wavefront measurement system 30 includes an imagesource 32, such as a laser, which projects a source image throughoptical tissues 34 of eye E so as to form an image 44 upon a surface ofretina R. The image from retina R is transmitted by the optical systemof the eye (e.g., optical tissues 34) and imaged onto a wavefront sensor36 by system optics 37. The wavefront sensor 36 communicates signals toa computer system 22′ for measurement of the optical errors in theoptical tissues 34 and/or determination of an optical tissue ablationtreatment program. Computer 22′ may include the same or similar hardwareas the computer system 22 illustrated in FIGS. 1 and 2. Computer system22′ may be in communication with computer system 22 that directs thelaser surgery system 10, or some or all of the components of computersystem 22, 22′ of the wavefront measurement system 30 and laser surgerysystem 10 may be combined or separate. If desired, data from wavefrontsensor 36 may be transmitted to a laser computer system 22 via tangiblemedia 29, via an I/O port, via an networking connection 66 such as anintranet or the Internet, or the like.

Wavefront sensor 36 generally comprises a lenslet array 38 and an imagesensor 40. As the image from retina R is transmitted through opticaltissues 34 and imaged onto a surface of image sensor 40 and an image ofthe eye pupil P is similarly imaged onto a surface of lenslet array 38,the lenslet array separates the transmitted image into an array ofbeamlets 42, and (in combination with other optical components of thesystem) images the separated beamlets on the surface of sensor 40.Sensor 40 typically comprises a charged couple device or “CCD,” andsenses the characteristics of these individual beamlets, which can beused to determine the characteristics of an associated region of opticaltissues 34. In particular, where image 44 comprises a point or smallspot of light, a location of the transmitted spot as imaged by a beamletcan directly indicate a local gradient of the associated region ofoptical tissue.

Eye E generally defines an anterior orientation ANT and a posteriororientation POS. Image source 32 generally projects an image in aposterior orientation through optical tissues 34 onto retina R asindicated in FIG. 3. Optical tissues 34 again transmit image 44 from theretina anteriorly toward wavefront sensor 36. Image 44 actually formedon retina R may be distorted by any imperfections in the eye's opticalsystem when the image source is originally transmitted by opticaltissues 34. Optionally, image source projection optics 46 may beconfigured or adapted to decrease any distortion of image 44.

In some embodiments, image source optics 46 may decrease lower orderoptical errors by compensating for spherical and/or cylindrical errorsof optical tissues 34. Higher order optical errors of the opticaltissues may also be compensated through the use of an adaptive opticelement, such as a deformable mirror (described below). Use of an imagesource 32 selected to define a point or small spot at image 44 uponretina R may facilitate the analysis of the data provided by wavefrontsensor 36. Distortion of image 44 may be limited by transmitting asource image through a central region 48 of optical tissues 34 which issmaller than a pupil 50, as the central portion of the pupil may be lessprone to optical errors than the peripheral portion. Regardless of theparticular image source structure, it will be generally be beneficial tohave a well-defined and accurately formed image 44 on retina R.

In one embodiment, the wavefront data may be stored in a computerreadable medium 29 or a memory of the wavefront sensor system 30 in twoseparate arrays containing the x and y wavefront gradient valuesobtained from image spot analysis of the Hartmann-Shack sensor images,plus the x and y pupil center offsets from the nominal center of theHartmann-Shack lenslet array, as measured by the pupil camera 51 (FIG.3) image. Such information contains all the available information on thewavefront error of the eye and is sufficient to reconstruct thewavefront or any portion of it. In such embodiments, there is no need toreprocess the Hartmann-Shack image more than once, and the data spacerequired to store the gradient array is not large. For example, toaccommodate an image of a pupil with an 8 mm diameter, an array of a20×20 size (i.e., 400 elements) is often sufficient. As can beappreciated, in other embodiments, the wavefront data may be stored in amemory of the wavefront sensor system in a single array or multiplearrays.

While the methods of the present invention will generally be describedwith reference to sensing of an image 44, a series of wavefront sensordata readings may be taken. For example, a time series of wavefront datareadings may help to provide a more accurate overall determination ofthe ocular tissue aberrations. As the ocular tissues can vary in shapeover a brief period of time, a plurality of temporally separatedwavefront sensor measurements can avoid relying on a single snapshot ofthe optical characteristics as the basis for a refractive correctingprocedure. Still further alternatives are also available, includingtaking wavefront sensor data of the eye with the eye in differingconfigurations, positions, and/or orientations. For example, a patientwill often help maintain alignment of the eye with wavefront measurementsystem 30 by focusing on a fixation target, as described in U.S. Pat.No. 6,004,313, the full disclosure of which is incorporated herein byreference. By varying a position of the fixation target as described inthat reference, optical characteristics of the eye may be determinedwhile the eye accommodates or adapts to image a field of view at avarying distance and/or angles.

The location of the optical axis of the eye may be verified by referenceto the data provided from a pupil camera 52. In the exemplaryembodiment, a pupil camera 52 images pupil 50 so as to determine aposition of the pupil for registration of the wavefront sensor datarelative to the optical tissues.

An alternative embodiment of a wavefront measurement system isillustrated in FIG. 3A. The major components of the system of FIG. 3Aare similar to those of FIG. 3. Additionally, FIG. 3A includes anadaptive optical element 53 in the form of a deformable mirror. Thesource image is reflected from deformable mirror 98 during transmissionto retina R, and the deformable mirror is also along the optical pathused to form the transmitted image between retina R and imaging sensor40. Deformable mirror 98 can be controllably deformed by computer system22 to limit distortion of the image formed on the retina or ofsubsequent images formed of the images formed on the retina, and mayenhance the accuracy of the resultant wavefront data. The structure anduse of the system of FIG. 3A are more fully described in U.S. Pat. No.6,095,651, the full disclosure of which is incorporated herein byreference.

The components of an embodiment of a wavefront measurement system formeasuring the eye and ablations may comprise elements of a WaveScann®system, available from AMO MANUFACTURING USA, LLC, MILPITAS, California.One embodiment includes a WaveScan system with a deformable mirror asdescribed above. An alternate embodiment of a wavefront measuring systemis described in U.S. Pat. No. 6,271,915, the full disclosure of which isincorporated herein by reference. It is appreciated that any wavefrontaberrometer could be employed for use with the present invention.Relatedly, embodiments of the present invention encompass theimplementation of any of a variety of optical instruments provided byAMO WaveFront Sciences, LLC, including the COAS wavefront aberrometer,the ClearWave contact lens aberrometer, the CrystalWave IOL aberrometer,and the like.

Relatedly, embodiments of the present invention encompass theimplementation of any of a variety of optical instruments provided byWaveFront Sciences, Inc., including the COAS wavefront aberrometer, theClearWave contact lens aberrometer, the CrystalWave IOL aberrometer, andthe like. Embodiments of the present invention may also involvewavefront measurement schemes such as a Tscherning-based system, whichmay be provided by WaveFront Sciences, Inc. Embodiments of the presentinvention may also involve wavefront measurement schemes such as a raytracing-based system, which may be provided by Tracey Technologies,Corp.

Optical Coherence Tomography (OCT)

Optical coherence tomography (OCT) system and methods may be used toascertain the location and orientation of the anatomical features withinthe eye (e.g., the anterior and posterior corneal surfaces, capsularbag, lens, and the like), either prior to, during, or after a surgicalprocedure. These data can be used to advantage in planning the surgicaltreatment. For example, in advanced LASIK planning, the location of thecritical refractive surfaces, in conjunction with wavefront data, can beused to customize the corneal ablastion. See, e.g., Mrochen et al.,“Optical ray tracing for the calculation of optimized corneal ablationprofiles in refractive treatment planning” J. Refract. Surg., April,24(4): S446-S451 (2008), the content of which is incorporated herein byreference. In some cases, such evaluation techniques can be performed incombination with a femtosecond laser treatment to create incisionswithin corneal tissue to form a LASIK flap. Other ophthalmic treatmentsinvolve procedures performed on anatomical features within the eye, suchas the capsular bag, lens, cornea, and the like. Such treatments mayinvolve the removal of cataracts. Embodiments of the present inventionencompass methods and systems for analyzing the ophthalmic anatomy of apatient via certain OCT techniques, and/or for providing therapeutictreatment to the ophthalmic anatomy. In some cases, techniques mayinvolve evaluating an ophthalmic anatomical feature of the eye, andoptionally operating a laser beam or providing some other therapeutictreatment modality to one or more of the anatomical features. Exemplarytherapeutic treatments (e.g. which may be performed with a femtosecondlaser or other device) include phacoemulsification, capsulorhexis,capsulotomy, and the like. Capsulotomy procedures generally refer toprocedure where the capsule is removed. Capsulorhexis procedures involvecutting of capsule and phacoemulsification procedures involvedisrupting, breaking up, or emulsifying the lens. Such treatments may beperformed as part of an extracapsular cataract extraction procedure(ECCE).

Embodiments of the present invention can be readily adapted for use withexisting laser systems and other optical treatment devices. Althoughsystem, software, and method embodiments of the present invention aredescribed primarily in the context of a laser eye surgery system, itshould be understood that embodiments of the present invention may beadapted for use in alternative eye treatment procedures, systems, ormodalities, such as spectacle lenses, intraocular lenses, accommodatingIOLs, contact lenses, corneal ring implants, collagenous corneal tissuethermal remodeling, corneal inlays, corneal onlays, other cornealimplants or grafts, and the like. Relatedly, systems, software, andmethods according to embodiments of the present invention are wellsuited for customizing any of these treatment modalities to a specificpatient. Thus, for example, embodiments encompass custom intraocularlenses, custom contact lenses, custom corneal implants, and the like,which can be configured to treat or ameliorate any of a variety ofvision conditions in a particular patient based on their unique ocularcharacteristics or anatomy.

A wide variety of OCT devices (e.g., spectral domain (SDOCT), sweptsource (SSOCT), time domain (TDOCT)) have been proposed, often involvingwhite light interferometers incorporating a light source that has widespectral width or which can be tuned rapidly over wide spectral range. Auseful review of OCT methods can be found in Wojtkowski, “High-speedoptical coherence tomography: basics and applications” Appl. Opt., June1, 49(16):D30-61 (2010), the content of which is incorporated herein byreference. Typically, the light is split into two components, one ofwhich serves as a reference and the other to probe the sample inquestion. The beams are recombined and produce an interference patternwhich is detected and analyzed to deduce range information. Theinterference pattern is produced when the recombined beams have a pathlength difference within the coherence length of the light source.Indeed this is what determines the depth resolution of the OCT system.In such cases of OCT, the depth resolution is determined by theeffective spectral breadth of the light source according to thefollowing equation.

$L_{c} = {\frac{2{\ln(2)}}{\pi\; n}\frac{\lambda}{\Delta\;\lambda}\lambda}$wheren=refractive indexλ=center wavelengthΔλ=spectral width (FWHM)

A super luminescent diode is often used to provide a wide spectral widthhaving good transverse coherence. In the case of SSOCT, the effectivespectral breadth is given by the tuning range of the swept source. Theinterference pattern can be detected in a number of ways. In SDOCT, theinterference is imposed as a modulation in the spectrum of the combinedreturn light and is detected by using spectrometer. In SSOCT, a narrowbandwidth source is tuned and the interference is imposed as a timemodulation on the combined return light and is detected with a balancedphotodiode. Likewise, the interference is a time modulation in TDOCTwhere the interference is created by varying the reference path length.

The depth range of the OCT systems can also depend on the OCT type. ForSDOCT, the depth range is limited by the spectral resolution of thespectrometer to a few millimeters. SSOCT systems have depth range thatis either limited by the k-frequency sample rate of the interferencesignal, or by the bandwidth of the narrow bandwidth laser sourceaccording to the equation above, whichever is shorter. TDOCT has anadvantage over most other OCT systems in that the depth range is limitedonly by the range over which the reference leg is varied; indeed,commercial devices using this method have been available for biometry ofthe eye; unfortunately, the required large motion of the reference pathcan introduce sufficient time for variations in the sample path due toeye motion, thus compromising the integrity of the measurement. Onlyrecently, through the use of specialized MEMS tunable vertical-cavitysurface emitting laser with long coherence length and a high speeddigitization circuit, has a depth range of tens of millimeters beenattained in combination with high speed OCT acquisition. Use of such OCTsystems has finally allowed full eye OCT imaging. See, e.g., Grulkowskiet al., “Retinal, anterior segment and full eye imaging using ultrahighspeed swept source OCT with vertical-cavity surface emitting lasers”,Biomedical Optics Express, November, 3(11):2733-51 (2012), the contentof which is incorporated herein by reference. Knupfer and Hauger havedescribed an OCT method comprised of two beams combined noncolinearly ona detector in U.S. Pat. No. 6,396,587, the content of which isincorporated herein by reference. Like many other OCT systems thebroadband source is split into reference and signal beams. The referenceand return signal beams are contained in optical fibers. These opticalfibers are simply directed toward a detector having a multiplicity ofpixels distributed in the plane containing both fibers. The lightemitted from the fibers produces a spatially compact interferencepattern modulated across the detector. The pattern is displaced alongthe detector according the path length difference between the referenceand return signal beams. Related systems are described in Hauger et al.,“Interferometer for Optical Coherence Tomography”, Applied Optics, Vol.42 Issue 19, pp. 3896-3902 (2003), the content of which is incorporatedherein by reference. It is noted that such systems involve non-lineardisplacement in the path difference.

Angle Multiplexed Optical Coherence Tomography (AMOCT)

As discussed elsewhere herein, angle multiplexed optical coherencetomography (AMOCT) systems and methods can involve the use of multipletest beams (optionally, with differing delays) which can be combinedwith a single reference beam on a single detector, for purposes ofevaluating the ocular anatomy of an individual patient. Embodimentsdisclosed herein involve the use of optics to linearize the interferencepattern displacement with path difference and the combination ofmultiple signal beams to provide simultaneous OCT measurements.According to some embodiments, individual test beams can be assignedrespective unique spatial frequencies. For example, it is possible toassign or correlate an individual test beam to a unique angle relativeto the reference beam. According to some embodiments, individual spatialfrequencies can be resolved from the detector signal using Fourieranalysis with matched filters, in a manner similar to how a radiooperates to isolate individual stations. Accordingly, AMOCT can involvethe simultaneous measurement of multiple test beams. According to someembodiments, where a return beam is weak compared to a reference beam,the fringes due to the signal beam interference are very weak and are ata different spatial frequency. According to some embodiments, returnreturn beams can be collected on multiple fibers, probing differentspatial or depth regions.

An analysis of multiple beam interference that follows includes ncollimated beams propagating in different directions, k_(j). As depictedin FIG. 5, multiple beams can be combined through a single collimatinglens on a single detector, though multiple collimation lenses could beused. This analysis yields the following equation for the detectedspatial intensity of the combined beams:

${I\left( {\omega,\overset{\rightarrow}{r}} \right)} = {{\sum\limits_{j}{{E_{j}(\omega)}}^{2}} + {\frac{1}{2}{\sum\limits_{j \neq l}\left\{ {{{E_{j}(\omega)}{E_{l}^{*}(\omega)}e^{i{\lbrack{{{({{\hat{k}}_{j} - {\hat{k}}_{l}})}\bullet\;\overset{\rightarrow}{r}\frac{\omega}{c}} + {({\phi_{j} - \phi_{l}})}}\rbrack}}} + {{E_{l}(\omega)}{E_{j}^{*}(\omega)}e^{- {i{\lbrack{{{({{\hat{k}}_{j} - {\hat{k}}_{l}})}\bullet\;\overset{\rightarrow}{r}\frac{\omega}{c}} + {({\phi_{j} - \phi_{l}})}}\rbrack}}}}} \right\}}}}$where E_(j) and ω are the electric field amplitude and the frequency ofeach beam, respectively, and c is the speed of light. The first term isthe incoherent sum of the beam intensities and the second term containsis the interferences between each beams. This equation is furthersimplified with a few definitions

${I\left( {\omega,\overset{\rightarrow}{r}} \right)} = {{\sum\limits_{j}{I_{j}(\omega)}} + {\sum\limits_{j \neq l}{\sqrt{{I_{j}(\omega)}{I_{l}(\omega)}}{\cos\left\lbrack {\left( {\frac{\Delta\;{\overset{\rightarrow}{k}}_{jl}\bullet\;\overset{\rightarrow}{r}}{c} + \tau_{jl}} \right)\omega} \right.}}}}$whereI_(j)(ω)=|E_(j)(ω)|²Δ{right arrow over (k)}_(j1)={circumflex over (k)}_(j)−{circumflex over(k)}_(l)τ_(jl)ω=ϕ_(j)−ϕ_(l)

The intensity of each beam is given by I_(J)(ω), Δk_(jl) is thedifference in propagation directions of each pair of beams, and τ_(jl)is the path delay difference (in units of time). This equation may berelevant to various OCT methods.

For the collinear methods of SDOCT, SSOCT and TDOCT, Δk_(jl). equals 0leaving

${I(\omega)} = {{\sum\limits_{j}{I_{j}(\omega)}} + {\sum\limits_{j \neq l}{\sqrt{{I_{j}(\omega)}{I_{l}(\omega)}}{\cos\left\lbrack {\tau_{jl}\omega} \right\rbrack}}}}$

The OCT signal for SDOCT is the spectrally resolved I(ω), SSOCT containsan implicit time dependence in ω(t) as the laser frequency is tunedyielding a time dependent signal, I(t). Finally, TDOCT contains avariable τ_(jl) as the reference path length is varied in time; in thiscase the detector integrates over all frequencies ω. In each case, themodulation depth of interference is twice the square root of the productof intensities.

The above equation involves a notable short coming of collinear OCTmethods—that the signals due to positive and negative delays are notdistinguishable. Indeed to distinguish between positive and negativedelays, some have proposed phase shift detection methods such as thatnoted by Wotjkowski et al., “Full range complex spectral opticalcoherence tomography technique in eye imaging” Optics Letters, Vol. 27,Issue 16, pp. 1415-1417 (2002), the content of which is incorporatedherein by reference. Such methods use weighted averages of five OCTimages with phase shifts in the reference path length. While improvingthe depth range and signal to noise ratio of these OCT methods, thistechnique has the drawbacks of requiring a precise phase shift mechanismlike a piezoelectric transducer, a stable path length to the sample, andreduces the overall acquisition rate by a factor of five.

Now consider the non-collinear case. Assuming without loss ofgenerality, that the beams propagate in the xz plane of our coordinatesystem, that the reference beam (the l^(th) beam) propagates along the zaxis and the j^(th) beam propagates at an angle θ_(jl) with respect tothe z axis, that the detector is located at z=0 and oriented along the xdirection and then the OCT equation equation simplifies. Note that likethe TDOCT case, the detector integrates over all frequencies yielding

${I(x)} = {{\int{\sum\limits_{j}{I_{j}(\omega)}}} + {\sum\limits_{j \neq l}{\sqrt{{I_{j}(\omega)}{I_{l}(\omega)}}{\cos\left\lbrack {\left( {\frac{x\;{\sin\left( \theta_{jl} \right\rbrack}}{c} + \tau_{jl}} \right)\omega} \right\rbrack}d\;\omega}}}$

The OCT signal is dependent on detector position, x, which acts like ascaled version of the time delay, τ_(jl). The x position represents atrue linear time delay induced by the non-colinearity of the beamswithout the sign ambiguity of other OCT methods. The spatial period ofthe interference signal produced by the j^(th) and l^(th) beams is givenby

${Period}_{jl} = {\frac{\omega\;{\sin\left\lbrack \theta_{jl} \right\rbrack}}{c} = {\frac{2\pi}{\lambda}{\sin\left\lbrack \theta_{jl} \right\rbrack}}}$where λ is the wavelength of the source. Thus we see that each pair ofbeams produces an interference signal with unique spatial period. Thereis a unique period adjustable by angle of propagation. Multiple beamscan be combined on a single detector, each pair of which produce an OCTinterference that can be separated from the others by virtue of itsunique spatial period. In the case of a narrowband source, theinterference signal extends across the detector, however, if the sourcehas sufficient bandwidth, then the interference signal is localizedabout the point where the reference and signal beam delays are equalwith an extent determined by the source coherence length.

According to some embodiments, AMOCT systems and methods may involvecombining a reference beam with the test beam at an angle to producespatial interference fringes. In some instances, a maximum range can beobtained when the spatial period is just resolved by the detector. Insome instances, if one fringe covers 4 pixels, then 4 pixels equal onewave (λ) of optical delay. In some instances, if the number of detectorsis N, then the useful AMOCT z range is N*λ/4. According to someembodiments, AMOCT can use a simple broadband source, such as an SLD.According to some AMOCT embodiments, the width of the fringe envelopecan be inversely related to the bandwidth of the source. According tosome embodiments, AMOCT systems and methods may involve monitoringmultiple beams. According to some embodiments, AMOCT systems and methodsmay involve the use of an optical delay that is rigorously linear in thedetector position. According to some embodiments, AMOCT systems andmethods may operate with no ambiguity with regard to positive andnegative relative delays.

OCT embodiments of the instant invention can be used to provide highlyprecise rangefinder limits which enable extremely accurate elevation mapevaluations. For example, certain OCT techniques can provide an accuracyfor range finding on the order of 10 microns, and thus provide improvedstandards of precision for corneal topography evaluations. In somecases, the incorporation of selected OCT techniques can eliminate orreduce the need for corneal topography fiducials during alignment byproviding accurate feedback to position optical equipment. As discussedelsewhere here, OCT embodiments can be used to characterize aspects ofthe corneal and other optical features, as well as other tissues.Corneal thickness (pachymetry) is a useful screening parameter toqualify patients for LASIK and other surgeries, and OCT approaches asdiscussed herein can enhance such measurements. Further, selected OCTtechniques can be used to supplement or provide improved biometricmeasurements of corneal stiffness (e.g., tonography). In some cases, theOCT systems and methods discussed herein can be used in ocular biometryfor advanced LASIK treatment planning and IOL fitting. Exemplary OCTtechniques can be used to measure anterior chamber depth, lensthickness, axial length, and other anatomical features of the eye.Further, exemplary OCT measurements can be combined with tomographicwavefront measurements and Purkinge data to model or evaluate individualeyes comprehensively.

Embodiments of the present invention provide OCT techniques where theoptical range is not limited by the resolution of the spectrometer ordetector, and where positive and negative displacements aredistinguishable with single measurements. Further, embodiments provideOCT techniques where the optical range is not limited by the detectorbandwidth, and where higher detector bandwidths can be used without acorresponding increase in noise levels. What is more, embodiments of thepresent invention provide OCT techniques where sensitivity is retainedat the extremes of the optical range, and where OCT signals withdifferent depth offsets can be measured simultaneously.

Single Signal-Reference Beam Pair

FIG. 4 illustrates aspects of angular multiplexed optical coherencetomography (AMOCT) systems and methods according to embodiments of thepresent invention. As depicted here, the AMOCT system 400 includes alight source 410. The light source may be provided as a single sourcelight mechanism, such as a super luminescent diode (SLD), which may befiber-coupled. In some cases, light from the light source can be coupledinto a fiber and split into two beams by a fiber coupler. As shown here,a fiber splitter 420 can be used to direct a signal or sample beam alonga sample leg 430 toward a test object 432 (such as an eye) and areference beam along a reference leg 440 toward a detector 442 such asan array detector. Here, the reference beam is delayed by running thereference beam through a delay mechanism 450. For example, the referencebeam can be delayed a fixed amount by running the beam throughadditional fiber length and/or free space. The signal beam 422 isretro-reflected from the test object 432 and re-injected into its fiber423. As shown here, the reference beam 424 is not retro-reflectedthrough its fiber nor is it recombined collinearly with the signal beamin the splitter. Rather, the reference beam is combined non-collinearlywith the retro-reflected signal beam in free space at location 460. Thesignal beam 422 light and the reference beam 424 light from theirrespective fibers 422 f, 424 f are combined on a lens 470. As shownhere, the lens 470 can provide a collimating function. Hence, the signaland reference beams emanating from their respective optical fibers canbe collimated by the lens. The wavefront from each of the divergingbeams can be considered as a non-planar wavefront (e.g. spherical). Byincorporating the collimating lens 470, it is possible to achieve alinear relationship between movement of the object 432 (e.g. eye)corresponding to the sample leg and movement of the fringe pattern onthe array detector 490. For example, the linear relationship can beprovided in a 1:1 ratio. That is, movement of the object results in acorresponding linear movement of the fringe pattern. The beat note orspatial period of the fringe pattern 480 can be determined by the angleθ between the combined signal and reference beams. By implementing thelens 470, it is possible to obtain a constant interference period acrossthe array detector, regardless of the position of the fringe pattern onthe detector. Hence, the location of the fringe pattern is accurate andthe resolution device is precise, at least partially as a result of thelens. As shown in FIG. 8, various lens configurations may be used.

With returning reference to FIG. 4, it can be seen that various timedelays may be implemented in the system. The interferometric aspects ofOCT techniques can depend on path differences between reference leglight and sample leg light. Such differences can be expressed in termsof time (e.g. delays) or distance (e.g. length). According to someembodiments, where differences in time are discussed, it is alsounderstood that differences in length may be similar. For example,individual optical fibers having different lengths may provide differentamounts of time delay due to the difference in propagation duration.Typically, OCT operates where there is little or no time delay ordifference in distance between sample and reference beams. For example,OCT may operate where the difference is within a range of a fewmillimeters. As shown here, τ1 may refer to a fixed time delay.According to some embodiments, the reference leg involves a fixed delay,and the sample leg involves a variable delay. In some cases, a sampleleg may involve a variable delay in addition to a fixed delay). In somecases, the 1 delay on the sample leg fiber depicted here is fixed. Afixed delay may be provided by a length of fiber and/or an air path,which provide no change. According to some embodiments, a localizedfringe pattern 480 is obtained when the net delay on the reference legis the same or substantially the same as the net delay on the sampleleg. Hence, a fringe pattern may result from a narrow region or band ofdelay at or near that equality (e.g. net sample leg delay=net referenceleg delay). According to some embodiments, a broadband light source isused for OCT, and the light coherently interferes over a distance thatis equal to the coherence length. A large bandwidth may correspond to ashort coherence length. According to some embodiments, the depthresolution may be determined by or dependent on the bandwidth of thelight source. According to some embodiments, a fringe pattern isproduced with the delay amount is within the coherence length of thelight source. Hence, for example, a fringe pattern may appear within a10 micron band (e.g. plus or minus 5 microns relative to a fixedreference leg delay). Where a short coherence length light source isused (e.g. wide or large bandwidth), the fringe pattern may be limitedto a narrow configuration that can be conveniently localized on adetector. In this sense, where one signal beam and one reference beamare used, the configuration can be considered to provide a singlesignal-reference beam pair configuration. A spatial separation oralignment offset between the fibers causes the collimated beams 422, 424to travel at an angle to each other at location 460. The tilt angle θoperates to produce a time delay between the beams 422, 424 that dependson transverse location. The beams 422, 424 produce an interferencefringe or localized fringe pattern 480 transverse to the propagationdirection that has high amplitude only in a region near where the beamdelays are sufficiently equal. Accordingly, a single signal-referencebeam pair in an AMOCT system can produce a transverse fringe pattern ata single frequency. As discussed elsewhere herein, the angle θ betweenthe two beams can confer or contribute to a particular beat note orspatial period in the interference.

AMOCT system 400 also includes a detection mechanism 490, such as alinear array detector. The detector can be provided with sufficientlysmall detector spacing, so as to sample the interfering beams along thefringe direction to capture the fringe pattern 480, and thus the “echo”signal associated with the signal-reference beam pair. The transverselocation of the maximum amplitude in the fringe pattern 480 can containthe depth information for the echo being detected. The fringe patternspatial frequency can be determined based on the center wavelength ofthe SLD, the distance between the fibers, and the focal length of thelens.

In cases where the reference beam 424 is much stronger than the signalbeam 422, the fringe pattern 480 may reside upon a large DC backgroundcaused primarily by the reference beam 424. In such cases, the smallfringe amplitude can be resolved and also demodulated by using a matchedfilter. This can be accomplished in the Fourier domain and result in ademodulated signal that peaks at the time delay corresponding to thedepth where the signal beam was reflected or scattered.

According to some embodiments, it is possible to combine multiple signalbeams with a single reference beam. Where individual signal beams haverespective unique carrier frequencies, and where different angles areused for individual signal beam, it is possible to simultaneouslymeasure fringes from multiple signal-reference pairs by using matchedfilters tuned to each carrier frequency. Such matched filters may bedesigned to preferentially transmit interference signals at spatialfrequencies about a single pair of beams while suppressing those fromother beam pairs. Because the linear detector can capture both thefringe amplitude and its phase, it is also possible to obtain enhanceddepth resolution when the AMOCT signal has sufficient fidelity.According to some embodiments, AMOCT systems can use the phaseinformation and provide depth resolution that is not limited to roughlyequal the coherence length of the light source.

According to some embodiments, the angle of the signal beam(s) relativeto the reference beam can be adjusted to approach, but not exceed, theNyquist frequency of the linear detector while being sufficientlydistinct in spatial frequencies such that the matched filters will allowtheir detection with little crosstalk. In some cases, at this limit, 4pixels in the detector would correspond to a full wave of relative delaybetween the reference and signal beams. For example, a system operatedat an SLD wavelength of 1 micron and a 8000 element detector would havea range span of 8000/4-2000 microns. Because an AMOCT system cansimultaneously sample multiple signal beams, the effective range of anAMOCT system can exceed that of some other tomography systems (e.g.spectral domain OCT) with as few as 3 multiplexed signal beams.According to some embodiments, desirable scanning depths can be achievedby using wavelengths between about 1.3 μm and about 1.5 μm.

Multiple Signal-Reference Beam Pairs

FIG. 5 illustrates aspects of angular multiplexed optical coherencetomography (AMOCT) systems and methods according to embodiments of thepresent invention. As depicted here, the AMOCT system 500 includes alight source 510. The light source may be provided as a single sourcelight mechanism, such as a super luminescent diode (SLD), which may befiber-coupled. In some cases, light from the light source can be coupledinto a fiber and split into two beams by a fiber coupler. As shown here,a fiber splitter 520 can be used to direct a signal or sample beam alonga sample leg 530 toward a test object 532 (such as an eye) and areference beam along a reference leg 540 toward a detector 542 such asan array detector. Here, the reference beam is delayed by running thereference beam through a delay mechanism 550. For example, the referencebeam can be delayed a fixed amount by running the beam throughadditional fiber length and/or free space. The signal beam 522 isscattered or reflected from the test object 532 and re-injected into itsfiber 523. The scattered or retro-reflected beam from the test object isthen passed through a fiber circulator 537, and into a fiber splitter539 which operates to divide the signal beam into multiple signal beams522 a, 522 b, and 522 c. As shown here, the reference beam 524 is notretro-reflected through its fiber nor is it recombined collinearly witha signal beam in the splitter. Rather, the reference beam is combinednon-collinearly with multiple retro-reflected signal beams in free spaceat location 560. The signal beams 522 a, 522 b, and 522 c and thereference beam 524 from their respective fibers are combined on a lens570. In this sense, where multiple signal beams and one reference beamare used, the configuration can be considered to provide a multiplesignal-reference beam pair configuration. A spatial separation oralignment offset between the fibers causes the collimated beams totravel at an angle to each other at location 560. The beams produce anoverlap 580 of localized fringe patterns transverse to the propagationdirection that has high amplitude only in a region near where the beamdelays are sufficiently equal. Accordingly, a multiple signal-referencebeam pair configuration in an AMOCT system can produce a complextransverse fringe pattern containing multiple frequencies.

As shown here, the sample leg signal beam can be separated by fibersplitter 539 and individual resulting beams processed with differentdelays (e.g. τ1, τ2, and τ3). Hence, different net sample delays can beassociated with respective location or angular differences relative tothe reference leg beam 524. As discussed elsewhere herein, an anglebetween two light beams can contribute to a beat note or interferencepattern or period. Here, where individual signal beams 522 a, 522 b, and522 c can have their own respective angle with the reference beam 524,it is possible to produce multiple beat notes or interference patternsor periods at the detector. For example, each signal-reference beam pairmay have a corresponding angle, and thus a corresponding beat note. Putanother way, where there are multiple signal beam fibers (e.g. emanatingfrom splitter 539), and such fibers are at varying angles relative tothe reference beam, then each signal-reference beam pair can produce alocalized fringe pattern having its own associated beat note.Accordingly, one or more beat notes can be controlled by adjusting thecorresponding angles of the signal-reference beam pairs. Whenconsidering the combined localized fringe patterns on the array detector(e.g. which may be overlapping with one another), it is possible toseparate out, extract, or otherwise isolate individual fringe patternstherefrom using Fourier or filter techniques. In this way, it ispossible to tune into a particular localized fringe pattern or channel,where each fringe pattern or channel is associated with a respectivesignal-reference beam pair angle, and where a spatial frequency of arespective fringe pattern or channel is a function of the respectiveangle. Relatedly, using these techniques it is possible to separate outor isolate interference patterns from one another. Accordingly,embodiments of the present invention encompass systems and methods fortuning into a certain beat note or associated fringe pattern or spatialperiod, and evaluating patient tissue at a depth corresponding to thatbeat note or fringe pattern or spatial period. For example, as shown inFIG. 5, the signal-reference beam pair of 522 b-524 corresponds to atissue depth at or near a posterior portion of the crystalline lens, andthus by analyzing the spatial frequency and/or fringe pattern associatedwith the 522 b-524 beam pair, it is possible to evaluate tissuecharacteristics of the posterior lens. As shown here, it is possible tosimultaneously detect multiple localized fringe patterns at the arraydetector. Hence, it is possible to simultaneously analyze patient tissueor related structures or interfaces at multiple depths simultaneously,and/or throughout a broad tissue depth range.

As depicted in FIG. 5, it is possible to use different channels to probeat various depths within the eye, or across a wide depth range withinthe eye. In some cases, a signal-reference beam pair may operate toprovide information throughout a depth range of about 5 mm to 10 mm. Theentire depth of the eye may be about 30 mm. Hence, by using such amultiplexed approach, which involves the simultaneous detection ofmultiple localized fringe patterns, each associated with a delay andangle, it is possible to evaluate much or all of the eye tissuesimultaneously. For example, evaluation of the anterior cornea can beassociated with τ1 and/or the 522 a-524 sample-reference angle,evaluation of the posterior lens can be associated with τ2 and/or the522 b-524 sample-reference angle, and evaluation of the retina can beassociated with τ3 and/or the 522 c-524 sample-reference angle. In thisway, it is possible to provide a system having multiple OCT subsystemson a single device, and various channels can be used to evaluate variousassociated tissue depths.

Dual Collection Fiber with Static Focus System

FIG. 6 illustrates aspects of angular multiplexed optical coherencetomography (AMOCT) systems and methods according to embodiments of thepresent invention. As depicted here, the AMOCT system 600 includes alight source 610. The light source may be provided as a single sourcelight mechanism, such as a super luminescent diode (SLD), which may befiber-coupled. In some cases, light from the light source can be coupledinto a fiber and split into two beams by a fiber coupler. As shown here,a fiber splitter 620 can be used to direct a signal or sample beam alonga sample leg 630 toward a test object 632 (such as an eye) and areference beam along a reference leg 640 toward a detector 642 such asan array detector. According to some embodiments, scattered lightcorresponding to various sections of the eye can be collected on twofibers (Fiber L and Fiber τ1) with high efficiency using a static focussystem. For example, Fiber L can serve to launch a probe beam such thatit focuses in the lenticular region and collects light scatteredtherefrom. Further, Fiber τ1 and Lens 2 can be positioned to efficientlycollect light scattered from the cornea and anterior chamber regionbecause very little light is blocked by Fiber L. Such imaging conditionscan provide high spatial resolution. One portion of the signal beamretro-reflected from the test object 632 is re-injected into Fiber L.Another portion of the signal beam retro-reflected from the test object632 is re-injected into Fiber τ1. Accordingly, the signal beam can bedivided into multiple signal beams 622 a, 622 b. As shown here, thereference beam 624 is not retro-reflected through its fiber nor is itrecombined collinearly with a signal beam in the splitter. Rather, thereference beam is combined non-collinearly with multiple retro-reflectedsignal beams in free space at location 660. The signal beams 622 a, 622b and the reference beam 624 from their respective fibers are combinedon a lens 670.

As depicted here, the τ1 fiber light is processed through both lens 1and lens 2. The τ2 fiber light is processed through lens 1 but not lens2. Often, on the sample side, light returning back toward the detectorcan be scattered by the surfaces or tissues which are beinginterrogated. Hence, such scattered light may provide a weakened lightsignal. As shown here, light which is directed toward the object tissueis focused by lens 1, toward the interrogated location. Using lens 1 andlens 2, the returning light can then be collimated and efficientlycollected into optical fiber for transmission toward the detector. Asshown in the example here, light can be focused at two depths within thepatient tissue, and respective returning light can be collected by twodifferent fibers. For example, evaluation of the anterior cornea can beassociated with 1 r and/or the 622 a-624 sample-reference angle, andevaluation of the posterior lens can be associated with τ2 and/or the622 b-624 sample-reference angle. In this way, it is possible toefficiently collect and process light associated with multiple depthswithin the patient tissue, thus providing an extend depth range.Although FIG. 6 depicts the use of two different fibers for twodifferent tissue depths, it is understood that multiple different fibers(e.g. more than two) can be used for evaluating multiple tissue depths(e.g. more than two). For example, a third fiber could be used toevaluate retinal tissue of the eye. In this way, it is possible toefficiently collect and process light associated with an extended depthrange throughout the eye (or tissue or anatomy) without the use of ascanning system that involves scanning a focus to different depthsthroughout the tissue or anatomy. That is, light can be efficientlycollected and processed for each individual channel, where a particularchannel is associated with a particular depth or depth range.

Multi-Point

FIG. 7 illustrates aspects of angular multiplexed optical coherencetomography (AMOCT) systems and methods according to embodiments of thepresent invention. As depicted here, the AMOCT system 700 includes alight source 710. The light source may be provided as a single sourcelight mechanism, such as a super luminescent diode (SLD), which may befiber-coupled. In some cases, light from the light source can be coupledinto a fiber and split into two beams by a fiber coupler. As shown here,a fiber splitter 720 can be used to direct one or more signal or samplebeams along a sample leg 730 toward a test object 732 (such as an eye)and a reference beam along a reference leg 740 toward a detector 742such as an array detector. Here, the reference beam is delayed byrunning the reference beam through a delay mechanism 750. For example,the reference beam can be delayed a fixed amount by running the beamthrough additional fiber length and/or free space. Individual signalbeams 722 a, 722 b, 722 c can be scattered or retro-reflected from thetest object 732 and re-injected into or otherwise directed intorespective fibers. As shown here, the reference beam 724 is notretro-reflected through its fiber nor is it recombined collinearly witha signal beam in the splitter. Rather, the reference beam is combinednon-collinearly with multiple retro-reflected signal beams 722 a, 722 b,722 c in free space at location 560. The signal beams 722 a, 722 b, and722 c and the reference beam 724 from their respective fibers arecombined on a lens 770. The beams produce an overlap 780 of localizedfringe patterns transverse to the propagation direction that has highamplitude only in a region near where the beam delays are sufficientlyequal. Hence, multiple signal-reference beam pairs can probe differenttransverse locations simultaneously. According to some embodiments, anAMOCT system can involve signal beams generated from different returnbeams, as in different locations on the cornea, but with small or nodelays between them. Such configurations can be used for multipointcorneal topography and simultaneous pachymetry. According to someembodiments, signal beam origins from various embodiments can becombined to enable biometric and multipoint CT and pachymetry.

According to some embodiments, a detection mechanism such as a lineararray detector may have multiple (e.g. up to four or more) linear arraysin each package. Such arrays may be similar to those used in colorscanner applications. The use of additional individual linear arrays canoperate to provide additional channels of detection.

In the embodiment depicted in FIG. 7, the sample leg involves multiplesignal beams 722 a, 722 b, 722 c at respective angles to object orpatient anatomy. Each of the associated signal beams have a common delay(e.g. τ1). Hence, it is possible to evaluate tissue at a certaindistance (e.g. across a common depth range for each channel), albeit atdifferent locations on the patient tissue. For example, it is possibleto probe or evaluate the cornea, at a given common depth, at differentlocations (e.g. three locations) across the cornea. In some cases, it ispossible to measure relative positions of different parts of the cornea.According to the embodiment shown here, it is possible to obtain cornealtopography information, such as shape information for the cornealsurface. In some cases, it is possible to measure or evaluate a commontissue or structure at different locations thereof. For example, usingthis technique it is possible to evaluate the iris at three differentlocations. Accordingly, this technique can be used for measuring orevaluating the tilt of the eye, including real-time measurements. Insome cases, this technique can be used to implement an eye trackingdevice or method (e.g. six axis eye tracker), whereby the eye positionand/or tilt can be evaluated, and used to determine laser ablation pulsedelivery protocols.

Sphero-Cylindrical Optical System and Linear Detector

FIG. 8 depicts aspects of angular multiplexed optical coherencetomography (AMOCT) systems and methods according to embodiments of thepresent invention. As shown here, a sphero-cylindrical optical systemcan provide a good match with a linear detector.

In use, the lens configuration shown here can operate to focus light sothat it impinged upon the array detector (e.g. linear CCD) in aconcentrated manner. The detector shown here is a line detectorconfiguration, with a short height (side view) and a long width (topview). Use of the cylindrical lens allows a large amount of light to beconcentrated on the detector, thus providing a highly efficient opticalsystem. As shown in the side view, light emanating from the test objectfiber and reference leg fiber combines to fill the spherical achromatlens, and is then focused tightly by the cylindrical achromat lens ontothe thin linear CCD detector. As seen in the top view, the object andreference fibers are angularly displaced from one another, and the lightis combined to fill the spherical achromat lens. However, thecylindrical achromat does not operate to diminish the width of thecombined beam in the same way that it operates to diminish the height ofthe combined beam. Accordingly, use of the cylindrical achromat allowsthe system to direct a large percentage of the combined light beams atthe linear CCD.

Simulations

The Laboratory Virtual Instrumentation Engineering Workbench (LabVIEW) asystem design platform and development environment was used to simulateaspects of AMOCT. In some instances, an interference pattern wascalculated for multiple beams. In some instances, individual beams wereassigned a respective power, angle, and relative delay. In someinstances, matched filters were created for individual signal-referencepairs. In some instances, a combined detector signal was Fourieranalyzed to extract the signals on each “channel”.

FIG. 9 depicts an exemplary detector signal simulation with sevenangularly combined signals at 50 μm delay increments.

In the simulation depicted in FIG. 10, individual signals have a carrierfrequency defined by their respective angle with the reference beam.Here the beam angle is 22.2 mR

As illustrated in the simulation of FIG. 11, Fourier analysis of thesignal can use filters tuned to individual carrier frequencies toresolve the individual signals. As shown here, various spatialfrequencies can be evaluated. According to some embodiments, a spatialperiod or beat note can refer to an interference period or a period ofan interference pattern. For example, when considering an interferencepattern with alternating bright and dark sections, the spatial periodcan refer to the separation between adjacent bright sections (or betweenadjacent dark sections). In some cases, a spatial period can beconsidered as a difference or modulation between two combined closelyrelated frequencies. For example, the spatial period can correspond to amodulation of intensity as measured by a detector.

In the simulation embodiment of FIG. 12, it can be seen that individualAMOCT signals are resolved with high fidelity.

FIG. 13 shows an exemplary simulation, where individual signals (e.g.seven) may overlap completely on the detector, thus leading to a complexfringe pattern.

As shown in the FIG. 14 simulation, Fourier analysis of the complexfringe pattern can allow the individual signals to be resolved.

As illustrated by these simulations and as discussed elsewhere herein,AMOCT techniques can provide simultaneous detection of multiple signalson a single detector, and lower implementation costs as compared withother OCT technologies. Further, AMOCT embodiments can be implementedwithout using gratings, moving parts, PZT elements, sophisticatedtunable light sources, or other features which may be associated withexisting OCT technologies. What is more, AMOCT implementations caninvolve multiple signals configured to sample a large depth range ormultiple selected smaller ranges. Still further, with certain AMOCTembodiments, there is no sign ambiguity in the tomography signalregarding the sign of the delay (e.g. positive and negative delays arehandled). As discussed elsewhere herein, it is possible to use AMOCT toobtain a large effective depth range useful in simultaneous anteriorchamber depth (ACD), lens thickness, axial length, or other opticalfeature measurements.

AMOCT systems and methods can be used in a variety of applications. Forexample, AMOCT can be incorporated with the use of femtosecond lasersystems and methods for ocular surgery. Further, it is possible to useAMOCT techniques to locate the anterior corneal surface and reference itdirectly. Relatedly, it is possible to use AMOCT techniques to replacecostly disposable standoff optics with lower cost, higher toleranceoptics. Still further, it is possible to use AMOCT techniques to detectthe crystal lens anterior or posterior surfaces for lens surgery. Whatis more, retinal surgeries associated with retinal re-attachment couldbe monitored in real time at multiple points during the surgery usingAMOCT systems and methods.

Arrayed Angle-Multiplexed Optical Coherence Tomography (AAMOCT)

As discussed elsewhere herein angle-multiplexed OCT (AMOCT) can be usedto acquire depth data from multiple regions simultaneously in a singlecycle with a single beam, using light of a wavelength amenable tosilicon detectors. In some cases, AMOCT techniques may involve scanningprocedures to obtain two dimensional b-scans or three dimensionalvolumes.

Arrayed angle multiplexed OCT (AAMOCT) systems and methods can involvethe integration of multiple interrogation beams into an AMOCT scheme.For example, a one dimensional array can be used to acquire a b-scan inone acquisition cycle, and a two dimensional array can be used to obtaina volumetric image in one cycle. This increased measurement throughputcan allow for near real-time observations to be made. In some instances,the increased measurement throughput can enable the extraction of anduse of aberrometry data. Due to the simultaneity of data acquisitionacross large volumes of the eye, AAMOCT is particularly suitable forapplications in corneal topography, pachymetry, cataractcharacterization and LCS planning, intraocular lens treatment planning,eye tracking, range finding, iris registration, and the like.

As depicted in FIG. 15, an exemplary AAMOCT system 1500 may include anintegrated optical circuit (IOC) that includes micro-arrayed objectivelenses, a waveguide, and optical circulators. Such An IOC device can beconnected via a fiber bundle to an angle multiplexor, conditioningoptics, and a CCD line detector. In some aspects, the system depicted inFIG. 15 can operate in an analogous way to the system depicted in FIG.7.

According to some embodiments, an AAMOCT system may include a onedimensional integrated optical circuit, optionally in combination withadditional scanning optomechanics to obtain volumetric data. In someembodiments, an AAMOCT system may include a two dimensional integratedoptical circuit. According to some embodiments, an AAMOCT system mayinclude the use of scanning optomechanics, for example if a single-spotsample density does not provide a sufficiently high spatial resolutionfor volumetric reconstruction. According to some embodiments, AAMOCTsystems and methods may involve the incorporation of phase delays at oneor more locations between reference and sample beams, for example in theintegrated optical circuit, the fiber bundle, and/or the multiplexor.

According to some AAMOCT embodiments, the spatial resolution achieved bythe system or method may be based on the based on the multitude oflenslets used. In some cases, each lenslet may operate to provide aseparate channel, for the angle multiplexing. In this way, it ispossible to interrogate multiple portions or spatial locationsthroughout the ocular structure, including the cornea, lens, retina, andthe like. Each individual lenslet of the lenslet array can provide arespective beam. Exemplary lenslet arrays can include any desired numberof lenslets, for example, 20, 100, or 1000 lenslets, where each lensletprovides a corresponding channel. In some cases, the system can operateto direct multiple sample beams toward the eye, such that differentbeams approach the eye at different angles (e.g. relative to an axis ofthe eye, such as the optical axis). In some cases, different beams canapproach the eye at the same angle. The various sample beam anglesimpinging upon the eye can be based on the configuration of the lensletarray and/or the angle of the light which is directed into the lensletarray for transmission therethrough.

As shown in FIG. 15, the sample beams directed toward the eye are moreor less parallel to one another, such that individual beams are directedto different portions of the eye. In some cases, one or more samplebeams may be angularly offset from one another. In some cases, thesystem provides scattered light corresponding to various tissuelocations, or various tissue or anatomical structure interfaces, and oneor more of the sample beams may or may not not have a normal incidencerelative to the corneal surface. According to some embodiments, theremay be variation in the angle of incidence for individual sample beamspropagated from the lenslet array toward the eye. In some cases,individual lenslets of the array may operate to focus light. In somecases, individual lenslets of the array may operate to collimate light.In some cases, one or more lenslets may have a common focal length. Insome cases, individual lenslets may have different focal lengths.Various related combinations and permutations of lenslet arrayconfigurations (including individual lenslet size, spacing, opticalpower, position, and the like) are encompassed by embodiments of thepresent invention. In some cases, one or move individual lenslets mayoperate to weakly focus light across a broad depth of tissue or anatomy.In some cases, two or more individual lenslets may operate to focuslight toward a common interrogation position, area, or depth range. Insome cases, individual lenslets may operate to interrogate respectivedepth positions or ranges.

According to some embodiments, one or move individual lenslets can havediameters at micron level dimensions. For example, an individual lensletmay have a diameter of about 100 microns. Larger and smaller lensletsizes are also contemplated. According to some embodiments, a fiberoptic array can be used to direct light toward the lenslet array. Often,such an array of fibers is offset from the lenslet array at a certaindistance. For example, the fiber array can be disposed one focal lengthaway from the lenslet array. In some cases, by varying the distance ororientation between the fiber array and the lenslet array, it ispossible to change the focus provided by the system. As shown here,multiple sample-reference beam pairs are angularly multiplexed at thedetector mechanism. The embodiment depicted in FIG. 15 is well suitedfor use in obtaining spatially resolved measurements across the eye atmultiple positions and/or depths simultaneously, without the use of ascanning mechanism (e.g. system involving galvanometrically controlledmirrors to provide dynamic angle adjustments). In some embodiments, thelenslet array may be a two dimensional array, for example a 10×10lenslet array, a 100×100 lenslet array, or the like. In some cases, alenslet array may provide individual lenslets that can be used todeliver interrogation beams across the entire diameter or area of theeye. In this way, it is possible to interrogate multiple points orpositions at one time, and to obtain a full snapshot of the eye at alllocations therethrough. Often, such systems may provide spatialresolution measurements involving an accuracy or precision on the orderof 20 microns.

AMOCT and AAMOCT techniques as disclosed herein are well suited for usein ophthalmological applications, as well as optical metrology, andsubcutaneous and vascular inspection applications, as well as subsurfaceinterrogation of any of a variety of materials, substances, orstructures.

The methods and apparatuses of the present invention may be provided inone or more kits for such use. The kits may comprise a system forevaluating an optical feature of a patient eye, and instructions foruse. Optionally, such kits may further include any of the other systemcomponents described in relation to the present invention and any othermaterials or items relevant to the present invention. The instructionsfor use can set forth any of the methods as described above.

Each of the calculations or operations described herein may be performedusing a computer or other processor having hardware, software, and/orfirmware. The various method steps may be performed by modules, and themodules may comprise any of a wide variety of digital and/or analog dataprocessing hardware and/or software arranged to perform the method stepsdescribed herein. The modules optionally comprising data processinghardware adapted to perform one or more of these steps by havingappropriate machine programming code associated therewith, the modulesfor two or more steps (or portions of two or more steps) beingintegrated into a single processor board or separated into differentprocessor boards in any of a wide variety of integrated and/ordistributed processing architectures. These methods and systems willoften employ a tangible media embodying machine-readable code withinstructions for performing the method steps described above. Suitabletangible media may comprise a memory (including a volatile memory and/ora non-volatile memory), a storage media (such as a magnetic recording ona floppy disk, a hard disk, a tape, or the like; on an optical memorysuch as a CD, a CD-R/W, a CD-ROM, a DVD, or the like; or any otherdigital or analog storage media), or the like.

All patents, patent publications, patent applications, journal articles,books, technical references, and the like discussed in the instantdisclosure are incorporated herein by reference in their entirety forall purposes.

While the above provides a full and complete disclosure of the preferredembodiments of the present invention, various modifications, alternateconstructions and equivalents may be employed as desired. Therefore, theabove description and illustrations should not be construed as limitingthe invention, which can be defined by the appended claims.

What is claimed is:
 1. An optical coherence tomography system,comprising: a detector comprising an array of pixels; a light sourceconfigured to supply a sample light beam to an eye and to further supplya reference light beam; an optical element configured to direct thereference light beam to the array of pixels; and an optical splitterconfigured to divide light returning from the eye into a plurality ofindividual signal beams each having a corresponding different pathlength from an output of the optical splitter to the optical element andeach corresponding to a respective different anatomical location of theeye, wherein each of the individual signal beams impinges on the opticalelement at a corresponding different angle with respect to the referencelight beam, and wherein the optical element is configured to direct theplurality of individual signal beams simultaneously to the array ofpixels.
 2. The optical coherence tomography system of claim 1, whereinthe detector is configured to detect individual unique interferencepatterns respectively provided by the plurality of individual signalbeams and the reference beam, for simultaneous evaluation of thedifferent anatomical locations of the eye.
 3. The optical coherencetomography system of claim 2, wherein unique interference spatialperiods of the unique interference patterns are adjustable in responseto changes in respective individual signal beam angles relative to thereference beam.
 4. The optical coherence tomography system of claim 1,wherein the optical element comprises one or more collimation lensesthat direct combined signal-reference beam pairs toward the detector. 5.The optical coherence tomography system of claim 1, wherein the systemprovide an accuracy for range finding on an order of 10 microns.
 6. Theoptical coherence tomography system of claim 1, further comprising afilter assembly that transmits interference signals at spatialfrequencies about a first signal-reference beam pair and suppressesinterference signals at spatial frequencies about a secondsignal-reference beam pair.
 7. A method of optical coherence tomography,comprising: supplying a sample light beam from a light source to an eye,and further supplying a reference light beam from the light source; anoptical element directing the reference light beam to a detectorcomprising an array of pixels; and an optical splitter dividing lightreturning from the eye into a plurality of individual signal beams eachhaving a corresponding different path length from an output of theoptical splitter to the optical element, and each corresponding to arespective different anatomical location of the eye, wherein each of theindividual signal beams impinges on the optical element at acorresponding different angle with respect to the reference light beam,and wherein the optical element directs the plurality of individualsignal beams simultaneously to the array of pixels.
 8. The method ofclaim 7, further comprising detecting, by the detector, individualunique interference patterns respectively provided by the plurality ofsample beams.
 9. The method of claim 8, further comprising evaluatingthe eye based on the detected interference patterns.
 10. The methodaccording to claim 9, further comprising positioning a cornealtopography system relative to the eye based on the evaluation, andobtaining a corneal topography measurement of the eye.
 11. The methodaccording to claim 10, wherein the topography measurement is performedwithout aligning the corneal topography system using corneal topographyfiducials.